Nomilin

There will be a series of articles on the topic in the near future, but for now, here is the scientifically established role of this completely unique fat loss pathway that has only recently come under the pharmacological spotlight:

Simply put, Nomilin is among the strongest naturally occurring TGR5 agonists on the planet. Agonism = activation, so nomilin activates the TGR5 pathway and should cause the above 6 effects, among others.

Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet.Ono E, Inoue J, Hashidume T, Shimizu M, Sato R.Author informationAbstract
TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids (BAs). TGR5 is thought to be a promising drug target for metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet (HFD). In the present study, we identified a naturally occurring limonoid, nomilin, as an activator of TGR5. Unlike BAs, nomilin did not exhibit the farnesoid X receptor ligand activity. Although the nomilin derivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a HFD for 9 weeks were further fed a HFD either alone or supplemented with 0.2%w/w nomilin for 77 days,nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance. Our results suggest a novel biological function of nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5.

Summary:

In vivo, nomilin activates TGR5 and reduces fat, blood glucose, and insulin. These are simultaneous fat loss + GDA properties. The data is below. Note that mice fed a high fat diet PLUS nomilin actually LOST bodyweight from when they first started despite the excessively high-calorie diet.

Nomilin as an anti-obesity and anti-hyperglycemic agent.Sato R.Author informationAbstract
Recent scientific findings support the notion that bile acids, which are cholesterol catabolites, are bioactive signaling molecules that function as ligands for the farnesoid X receptor or a G-protein-coupled receptor, TGR5. Through these receptors, bile acids can maintain not only bile acid homeostasis but also lipid and carbohydrate homeostasis. An intriguing finding regarding the role of TGR5 in energy metabolism and glucose homeostasis suggests a potential approach to combat obesity and insulin resistance by targeting this receptor to increase thermogenesis and incretin secretion. In this review, I have summarized the latest findings related to TGR5 agonists, in particular, a citrus limonoid, nomilin, and the roles of these agonists in energy metabolism and glucose homeostasis.

The author deems nomilin one of the few future natural products to pursue for combating the obesity epidemic:

Studies on the constituents of edible and medicinal plants. III. Effects of seven limonoids on the sleeping time induced in mice by anesthetics.Wada K, Yagi M, Kurihara T, Haga M.Author informationAbstract
Effects of seven limonoids, obakunone (1), 7 alpha-obakunol (2), 7 beta-obakunol (3), limonin (4), 7 alpha-limonol (5), 7 beta-limonol (6) and nomilin(7), on the sleeping time induced in mice by anesthetics were assayed. All the limonoids, except for 2, shortened the sleeping time induced by alpha-chloralose and urethane. 7 gave the highest reduction rate of sleeping time, and the order of the reduction rate of sleeping time was as follows; 7 > 1 and 3 > 4, 5 and 6. As the chemical structures of these compounds are similar to each other, the relationship between the structure and the effects of limonoids on sleeping time was discussed.

Summary:

Nomilin (7) was the strongest “stimulant” out of all tested limonoids, capable to reducing sleep-time induced by tranquilizers/sedatives by the largest margin.

Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system.Raphael TJ, Kuttan G.Author informationAbstract
The effect of naturally occurring triterpenoid compounds such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin on the immune system was studied using Balb/c mice. Intraperitoneal treatments with 5 doses of these terpenoid compounds were found to enhance the total white blood cells (WBC) count. In ursolic acid, oleanolic acid and nomilin treated animals the maximum total WBC count was observed on the 6th day, while in glycyrrhizic acid treated animals it was observed only on the 9th day after the drug treatment. In ursolic acid, oleanolic acid and nomilin treated animals the percentage of increase in the total WBC count was to 91.48 +/- 4.6%, 135.75 +/- 6.4% and 117.33 +/- 17.9% respectively. In the glycyrrhizic acid treated animals the total WBC count was increased to 114.9 +/- 18%. Bone marrow cellularity and alpha-esterase positive cells were also enhanced by the treatment with these terpenoids. Treatment with various triterpenoids along with antigen produced an enhancement in the specific antibody titre and the number of plaque forming cells (PFC) in the spleen. Triterpenoids remarkably inhibited delayed type hypersensitivity reaction (DTH). These results indicate the immunomodulatory activity of naturally occurring triterpenoids such as glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin.

Summary: Nomilin over DOUBLED the amount of WBCs as part of the immune response. This indicates strong immune system stimulation.

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The above is my own opinion and does not reflect the opinion of PES